HHS Charged with Bungling Preemie Study

Public Citizen, the watchdog group founded by Ralph Nader, today demanded an apology from Kathleen Sebelius, secretary of the Department of Health and Human Services (HHS), for what it termed HHS mishandling of informed consent in a federally-funded study evaluating oxygen saturation targets in premature infants.

The group claimed in a letter to HHS that the agency's Office for Human Research Protections (OHRP) failed to respond appropriately when it uncovered deficiencies in the consent forms used by the trial's participating centers; those problems are blamed for leaving the infants' parents uninformed about the potential risks of the trial and the actual purpose of the research. Public Citizen said the infants' parents should receive a formal apology.

"While OHRP appropriately documented the serious informed-consent deficiencies related to the lack of disclosure of the risks of the research, the scope of OHRP's compliance-oversight findings for this research and the corrective actions being required by the agency are grossly inadequate," read Public Citizen's letter, which was signed by deputy director Michael Carome and director Sidney Wolfe, MD, of the organization's Health Research Group.

The study in question is the SUPPORT trial, which was funded by the NIH and conducted at 23 U.S. centers from 2005 to 2009. It included 1,316 extremely premature infants who were randomized to either a lower oxygen saturation target of 85% to 89% or a higher oxygen saturation target of 91% to 95%. The primary outcome was a composite of retinopathy of prematurity, death before hospital discharge, or both.

The trial did not include a control group that received usual care, which entails individualized adjustment of the oxygen saturation levels within the entire range from 85% to 95%.

"Through randomization, subjects were changed from what would have been individualized oxygen management had they not participated in the study to different fixed target levels of oxygen management, independent of perceived clinical need or an individualized assessment of risks and benefits," according to Public Citizen.

The results of the trial showed that infants in the lower-saturation group had a lower rate of severe retinal problems (8.6% versus 17.9%; RR 0.52, 95% CI 0.37 to 0.73), but a higher rate of death (19.9% versus 16.2%; RR 1.27, 95% CI 1.01 to 1.60) compared with those in the higher-saturation group.

Last month, OHRP sent a letter to one of the participating centers -- the University of Alabama at Birmingham -- detailing problems with the consent forms used; specifically, the forms failed to sufficiently explain the potential risks of retinopathy of prematurity or death with using the experimental lower or higher oxygen saturation targets. All of the other participating centers had similar problems with their consent forms and were copied on the letter from OHRP.

"The failure to disclose such critically important information undoubtedly directly affected parents' decisions to enroll their premature infants in this study," according to Public Citizen. "It is highly likely that had they been appropriately informed about the nature of the research and its risks, many, if not most, parents would have declined to enroll their extremely premature infants in the SUPPORT study."

"As a result of these deficiencies in the informed-consent process, the investigators of the SUPPORT study failed to obtain the legally effective informed consent from the subjects' parents, and the conduct of the study was highly unethical," the group wrote.

But Public Citizen said that OHRP failed to require "meaningful corrective actions by HHS."

"Because this study was funded by NIH, the Department of Health and Human Services now has a moral obligation to formally apologize to the parents of all subjects enrolled in the study," the group wrote, adding the the apology should include complete disclosure of the purposes of the study, the experimental nature of the interventions, and the risks.

Beyond the apology, Public Citizen also wants Sebelius to direct OHRP to require all of the participating centers to take action to avoid informed consent problems in the future, initiate an independent investigation into "how the HHS system for review and oversight of human subjects research failed so miserably," determine ways to prevent similar problems in the future, and identify and stop any unethical ongoing research involving premature infants.

HHS did not respond to a request for comment by the time of story publication.

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